View source for Neurula

{{short description|Embryo at the early stage of development in which neurulation occurs}}
[[File:Vetebrate Embryo.jpg|thumb|Cross section of a vertebrate embryo in the neurula stage]]
A '''neurula''' is a [[vertebrate]] [[embryo]] at the early stage of development in which [[neurulation]] occurs. The neurula stage is preceded by the [[gastrula]] stage; consequentially, neurulation is preceded by [[gastrulation]].<ref name=":1">{{cite journal |last1=Stern |first1=Claudio D. |title=Initial Patterning of the Central Nervous System: How Many Organizers? |journal=Nature Reviews Neuroscience |date=February 2001 |volume=2 |issue=2 |pages=92–98 |url=https://www.ucl.ac.uk/biosciences/departments/cdb/people/claudio-stern/stern_lab/NNR.pdf |doi=10.1038/35053563 |pmid=11252999 |s2cid=13652379 }}{{Dead link|date=April 2023 |bot=InternetArchiveBot |fix-attempted=yes }}</ref> Neurulation marks the beginning of the process of [[organogenesis]].<ref name=":0">{{cite journal|last1=Andrews|first1=R. M.|date=2004|title=Patterns of embryonic development|url=https://pdfs.semanticscholar.org/5bba/4ca82902c281de47776f7db83e2506e473f1.pdf|archive-url=https://web.archive.org/web/20181130202324/https://pdfs.semanticscholar.org/5bba/4ca82902c281de47776f7db83e2506e473f1.pdf|url-status=dead|archive-date=2018-11-30|journal=Reptilian Incubation: Environment, Evolution and Behaviour|pages=75–102|s2cid=42246488 }}</ref>
Mice, chicks, and frogs are common experimental models for studying the neurula. Depending on the species, embryos reach the neurula stage at different time points and spend a varying amount of time in this stage.<ref name=":3" /><ref name=":8" /> For [[Oviparity|oviparous]] organisms, incubation temperature also affects the length of neurulation.<ref name=":0" /> In addition to development of the [[neural tube]], other processes occur in a neurula stage embryo depending on the species. For example, in reptiles, [[Extraembryonic membrane|extra-embryonic membrane]] tissues become distinct from the embryo.<ref name=":0" />
The neurula embryo has five regions of [[mesoderm]] that surround the neural tube.<ref name=":9" /> Anterior mesoderm develops into the head region, while posterior mesoderm develops into the trunk.<ref name=":1" /> Various molecules, including [[proteoglycan]]s in the [[extracellular matrix]], and genes, including [[Pax genes|Pax]] transcription factors, are essential for the development and closure of the neural tube in the neurula stage embryo.<ref name=":4" /><ref name=":7" />
== Neurulation ==
[[Neurulation]] is a process in vertebrate embryos at the neurula stage in which the [[neural tube]] is formed.<ref name=":4">{{Cite journal|last1=Fleming|first1=A|last2=Gerrelli|first2=D|last3=Greene|first3=N D|last4=Copp|first4=A J|date=2002-03-01|title=Mechanisms of normal and abnormal neurulation: evidence from embryo culture studies.|url=http://www.ijdb.ehu.es/web/paper.php?doi=9184327|journal=International Journal of Developmental Biology|volume=41|issue=2|issn=0214-6282}}</ref><ref name=":5">{{Cite web|url=http://biology.kenyon.edu/courses/biol114/Chap14/Chapter_14.html|title=Chapter 14. Gastrulation and Neurulation|last=Slonczewski|first=Joan|website=biology.kenyon.edu|access-date=2018-11-16}}</ref> There are two types of neurulation: [[primary neurulation|primary]] and [[secondary neurulation]]. Primary neurulation refers to the formation and inward folding of the neural plate upon itself to form the neural tube.<ref name=":4" /><ref name=":5" /> In secondary neurulation, the neural tube forms via the merging of cavities in the medullary cord.<ref name=":4" /><ref name=":5" /><ref>{{Cite journal|last1=Shimokita|first1=Eisuke|last2=Takahashi|first2=Yoshiko|date=April 2011|title=Secondary neurulation: Fate-mapping and gene manipulation of the neural tube in tail bud|journal=Development, Growth & Differentiation|volume=53|issue=3|pages=401–410|doi=10.1111/j.1440-169x.2011.01260.x|pmid=21492152|s2cid=31342085 |issn=0012-1592|doi-access=}}</ref> In amphibians and reptiles, primary neurulation forms the whole neural tube, and the neural tube closes simultaneously along its length.<ref name=":5" /> Contrarily, in fish, secondary neurulation forms the neural tube.<ref name=":6">{{Citation|last1=Schoenwolf|first1=Gary C.|title=Mechanisms of Neurulation|volume=136|date=2000|work=Developmental Biology Protocols|pages=[https://archive.org/details/developmentalbio00rock/page/125 125–134]|publisher=Humana Press|doi=10.1385/1-59259-065-9:125|pmid=10840705|isbn=978-1592590650|last2=Smith|first2=Jodi L.|url-access=registration|url=https://archive.org/details/developmentalbio00rock/page/125}}</ref> Both primary and secondary neurulation occur in birds and mammals, although with slight differences. Primary neurulation occurs in the cranial and upper spinal regions, which gives rise to the brain and upper regions of the spinal cord. Secondary neurulation occurs in the lower sacral and caudal regions, resulting in the formation of the lower regions of the spinal cord.<ref name=":4" /><ref name=":6" /> In birds, the neural tube closes anterior to posterior, while in mammals, the middle closes first, followed by the closure of both ends.<ref name=":5" />
== Developmental timing ==
The point at which the embryo reaches the neurula stage differs among species, while for oviparous organisms, the length of neurulation is additionally affected by incubation temperature. In general, the lower the temperature, the greater the length of neurulation. Chick embryos reach the neurula stage on day 2 post-fertilization, and they undergo neurulation up to day 5. Reptiles, including crocodiles, lizards, and turtles, tend to spend a longer time in the neurula stage.<ref name=":0" /> A typical frog embryo, incubated at 18&nbsp;°C, is an early stage neurula by 50 hours post-fertilization and a late stage neurula by 67 hours.<ref name=":3">Hill, M.A. (2018, November 30) '''Embryology''' ''Frog Development''. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Frog_Development .</ref> The mouse embryo begins neurulation on day 7.5 of gestation and remains in the neurula stage until day 9.<ref name=":8">Hill, M.A. (2018, November 30) '''Embryology''' ''Mouse Timeline Detailed''. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Mouse_Timeline_Detailed .</ref>
== Morphology ==
The [[mesoderm]] of a vertebrate embryo in the neurula stage can be divided into five regions. Ventral to the [[neural tube]] is the [[Axial mesoderm|chordamesoderm]]. Lateral to either side of the neural tube is the [[paraxial mesoderm]], while the intermediate lateral region to the neural tube is the [[intermediate mesoderm]]. The fourth region is the [[lateral plate mesoderm]], and the last region is the head mesenchym.<ref name=":9">{{Cite journal|last=Gilbert|first=Scott F.|date=2000|title=Paraxial and intermediate mesoderm|url=https://www.ncbi.nlm.nih.gov/books/NBK9997/|journal=Developmental Biology. 6th Edition}}</ref> Anterior portions of the mesoderm develop into rostral regions of an organism, such as the head, while posterior mesoderm develops into caudal regions, such as the trunk or tail.<ref name=":1" /> The paraxial mesoderm, also termed somitic mesoderm, develops into [[somite]]s, blocks of tissue that occur in a segmental pattern. Somites, in turn, give rise to vertebrae, ribs, skeletal muscle, cartilage, tendons, and skin.<ref name=":5" /><ref>Larsen, William J. (2001). ''Human embryology'' (3. ed.). Philadelphia, Pa.: Churchill Livingstone. pp. 53–86. {{ISBN|0-443-06583-7}}.</ref>
[[File:Comparative embryology of the vertebrates; with 2057 drawings and photos. grouped as 380 illus (1953) (20047812224).jpg|thumb|Transition from the gastrula stage to the neurula stage]]
In ''Xenopus laevis'', the transition from the gastrula to the neurula involves morphological changes in two regions surrounding the blastopore: the dorsal involuting marginal zone (IMZ) and the overlying non-involuting marginal zone (NIMZ) of the gastrula. Following involution at the mid-gastrula stage, the IMZ undergoes [[convergent extension]], in which the lateral regions narrow and move towards the midline and the anterior end lengthens. This has the effect of narrowing the [[Gastrulation|blastopore]]. The NIMZ, which does not involute, simultaneously extends in the opposite direction and at a greater rate to cover regions no longer occupied by the IMZ. The convergent extension of the IMZ and NIMZ begins in the second half of gastrulation and continues into the late neurula stage. Eventually, deep tissue of the IMZ forms the central [[notochord]] and the surrounding [[paraxial mesoderm]]. By the early neurula stage, the notochord is clearly distinguished. Notochordal cells become arranged in a formation representing a stack of coins in a process termed circumferential intercalation. The superficial layer of the IMZ develops into the roof of the [[archenteron]], or the primitive gut, while the underlying [[endoderm]] forms the archenteron floor. The NIMZ develops into a structure resembling the early [[neural tube]]. The outer ectodermal layer of the neurula is formed by uniform expansion of the cells at the [[Polarity in embryogenesis|animal pole]], known as the animal cap. The [[ectoderm]] then differentiates into [[Nervous system|neural]] and [[Epidermis|epidermal]] tissue.<ref name=":2">Keller, R. E., Danilchik, M., Gimlich, R., & Shih, J. (1985). [http://dev.biologists.org/content/develop/89/Supplement/185.full.pdf "The function and mechanism of convergent extension during gastrulation of Xenopus laevis]" (PDF). ''Development'', ''89''(Supplement), 185-209.</ref>
In reptilian embryos, beginning in the late-stage neurula and carrying over into the early stages of organogenesis, [[Extraembryonic membrane|extra-embryonic membrane]] tissues comprising the [[yolk sac]], [[chorion]], and [[amnion]] become distinct from the tissues of the embryo. The [[mesoderm]] splits to create the extra-embryonic coelom, which consists of two layers. The vascularized mesoderm-endoderm inner layer, termed the splanchnopleure, develops into the yolk sac, while the nonvascularized ectoderm-mesoderm outer layer, termed the somatopleure, becomes the amnion and chorion. During organogenesis, these three extra-embryonic tissues become fully developed. Additionally, within the reptilian neurula, tissues of the brain begin to differentiate and the heart and blood vessels start to form.<ref name=":0" />
== Chemical composition ==
Mouse neurula tissues divide rapidly, with an average [[cell cycle]] lasting 8–10 hours. [[Proteoglycan]]s in the [[extracellular matrix]] (ECM) of neurula-stage cells play an important role in promoting functional cranial neurulation and neural fold elevation; [[hyaluronic acid]] (HA) is synthesized and becomes accumulated, while the cell maintains a low level of sulfated [[glycosaminoglycan]]s (GAGs). HA is involved in creation of biconvex neural folds, while sulfated GAGs are critical in manipulating the neural groove into a V-shape, as well as in neural tube closure. The ECM does not play a major role in spinal neurulation due to the close-packed nature of the mesodermal cells in the spinal region, which allows little intercellular space. Additionally, actin-containing microfilaments are believed to be necessary in cranial neurulation. They may act as the mechanism for neural folding, or they may stabilize neural folds that have already formed; however, their exact role has not been determined. There is some evidence that [[growth factor]]s, such as [[insulin]] or [[transferrin]], also play a role in neurulation, but this link has not been well-studied.<ref name=":4" />
== Gene activation ==
A variety of genes have been found to be expressed in the neurula stage embryo. Different genes are activated for different neurulation events, such as those occurring in separate regions of the developing neural tube.<ref name=":4" /> These genes are necessary for proper neurulation and closure of the neural tube. Signaling molecules such as [[Wnt signaling pathway|Wnts]], [[Fibroblast growth factor|FGFs]], and [[BMF (gene)|BMFs]] along with the transcription factors that include [[MSX1|Msx]], [[SNAI1|Snail]][[SNAI2|s]], [[SOX gene family|Sox8/9/10]], and [[PAX3|Pax3]][[PAX7|/7]] genes play key roles in neural crest formation.<ref name=":4" />
[[Pax genes|Pax]] transcriptional factors have an important role in early development, especially with regards to the [[Central nervous system|CNS]] and neural crest. Pax3 and Pax7 are promoters of both neural crest cell survival along with promoting environmental stress resistance.<ref name=":7">{{Cite journal|last=Monsoro-Burq|first=Anne H.|date=2015-08-01|title=PAX transcription factors in neural crest development|journal=Seminars in Cell & Developmental Biology|volume=44|pages=87–96|doi=10.1016/j.semcdb.2015.09.015|pmid=26410165|issn=1084-9521}}</ref> In mouse embryos Pax3 blocks the [[Tumor suppressor|tumor suppressor gene]] [[p53]], which is necessary for controlled proliferation and genomic stability, is expressed in all cells of the neurula.<ref name=":4" /><ref name=":7" /> During early development Pax3 is expressed at the posterior and lateral area of the neural plate, the same region that the neural crest arises from.<ref name=":7" /> Neural crest defects were found to occur in mouse and human Pax3 mutants, indicating an importance of functionality.<ref name=":7" /><ref>{{Cite journal|last1=Tassabehji|first1=Mayada|last2=Read|first2=Andrew P.|last3=Newton|first3=Valerie E.|last4=Harris|first4=Rodney|last5=Balling|first5=Rudi|last6=Gruss|first6=Peter|last7=Strachan|first7=Tom|date=1992-02-13|title=Waardenburg's syndrome patients have mutations in the human homologue of the Pax-3 paired box gene|journal=Nature|volume=355|issue=6361|pages=635–636|doi=10.1038/355635a0|pmid=1347148|bibcode=1992Natur.355..635T |s2cid=4330804 |issn=0028-0836}}</ref> Within chicks, frogs and fish Pax3/Pax7 are activated by Wnt and FGF signaling.<ref name=":7" /> Pax3 and Pax7 are also required for neural crest induction after depletion of the two genes resulted in the lack of activation of the specific neural crest genes Snail2 and [[FOXD3|Foxd3]], which didn't allow further development or emigration of neural crest.<ref name=":7" /> Using knockouts has been helpful for understanding the role and functions of several genes found in the neurula. For example, [[WNT1|Wnt-1]] was found to have no role in the closing of the neural plate, despite being present at the tip of the neural folds when it is closing. Though mutants of Wnt-1 does lead to pattern defects within the brain. [[Notch 1|Notch1]] is involved with formation of somites. [[Hepatocyte nuclear factors|HNF-3]] is needed for development of the notochord and node.<ref>{{Cite journal|title=Subconjunctival auto-hemotherapy of eye burns in our cases|journal=Klinika Oczna|volume=94|issue=4|pages=113–4|pmid=1405409|date=2012-03-17|doi=10.4016/46352.01|last1=Lenkiewicz|first1=E.|last2=Ferencowa|first2=A.|last3=Szewczykowa|first3=E.}}</ref> The gene [[Apolipoprotein B]], which is involved in transporting and metabolizing fat soluble molecules in the blood, is expressed in the yolk sac and fetal liver.<ref name=":4" /> Within the neurula in ''Xenopus laevis,'' development genes Xwnt-3 and Xwnt-4 are present.<ref>{{Cite journal|date=1991-02-01|title=Isolation of cDNAs partially encoding four XenopusWnt-1int-1-related proteins and characterization of their transient expression during embryonic development|journal=Developmental Biology|volume=143|issue=2|pages=230–234|doi=10.1016/0012-1606(91)90073-C|issn=0012-1606|last1=Christian|first1=Jan L.|last2=Gavin|first2=Brian J.|last3=McMahon|first3=Andrew P.|last4=Moon|first4=Randall T.|pmid=1991549 }}</ref>
== References ==
<references />
{{Development of nervous system}}
[[Category:Embryology of nervous system]]